Big-bottomed sheep a genetic mystery

15 September 2002: Having an oversized bottom for many is a source of embarrassment but for one flock of genetically unique sheep, their generous backsides make them immune to being the butt of jokes.

Scientists from the U.S. Department of Agriculture and Duke University in Durham reported Monday they have discovered an elusive mutated gene that causes some sheep to have unusually muscular and large rear ends. What makes this mutated gene so important is it could help explain how muscle and fat are distributed in these animals and possibly in other mammals as well -- including humans.

The gene is called callipyge, which means "beautiful buttocks" in Greek. The callipyge gene is a so-called "stealth gene," meaning it was more difficult to track down through traditional genetic mapping methods.

Scientists are excited about this callipyge gene for its potential to teach them more about the processes that lead to fat metabolism and obesity, a major public health epidemic in the United States. Having such large muscular bottoms could be a beneficial trait because it enables the animals to convert what they eat into muscle almost one-third more efficiently than regular sheep.

What also makes this finding a curiosity is the callipyge sheep are born a normal size at birth and then bulk up in the rear as they develop. The gene is expressed in the animal's bottom but "it's not only in the rear end muscles it's also in the loins ... so the whole animal is bigger," co-author Randy Jirtle, professor of radiation oncology at Duke, told United Press International.

Although researchers have located the mysterious callipyge gene, it's unclear how exactly it triggers this unusual trait of large, muscular bottoms. Jirtle explained scientists already knew about a nearby gene called DLK-1, which is over-expressed in the rear ends of these callipyge genes.

However, what is curious is that DLK-1 has no known mutations. Jirtle said scientists suspect the callipyge gene might be improperly regulating DLK-1, which then somehow stunts fat cells from maturing normally in the sheep's hind quarters.

"There's no doubt this is an important switch," Jirtle said. If these suspicions prove true with further study, this finding could indicate "these genetic disorders might not due to single gene."

Instead, genetic diseases might be the result of a single gene that's responsible for overseeing a region of genes. If that single gene mutates, it could trigger a domino effect over the other genes it regulates, Jirtle explained.

What is critical is how important a role that gene region has. "It's the difference between shutting down Chicago and shutting down Raleigh-Durham," Jirtle said.

In addition to opening doors for scientists to better understand of stealth genes, muscle distribution and fat metabolism, the research also could enhance livestock breeding for meat production, though Jirtle said these large-bottom sheep wouldn't make a tasty entrée.

"The disadvantage in this situation is the fat cells are immature, so there's no fat," he said. "(Meat is) drier and as a consequence to people, it tastes tougher."

Max Rothschild, a professor of animal sciences at Iowa State University in Ames and coordinator of the USDA's National Pig Genome Mapping Project, said the behavior of this callipyge gene poses more questions than answers.

"This is a big area," Rothschild told UPI. "We're just starting to scratch the surface. All these are pathways that we need to understand. We need to understand how the genes work and how they communicate (to one another)."

Rothschild cautioned that although a gene initially may be perceived to offer a positive trait, such as converting food into muscle more efficiently, genes can be a double-edged sword. There could be "antagonist effects in other traits" from a gene that also produces beneficial traits.

This finding also could help treat human conditions, though Rothschild pointed out "this is way off."

Genes that help produce muscle could be used among HIV and cancer patients, he said, which in turn could help them better endure their medical treatments.

"Once you know a gene has a certain effect," he said, "from a pharmacological way you can look at the targets that could affect that gene."